AlM:To investigate the features on prolonged central serous chorioretinopathy ( CSCR ) by optical coherent tomography ( OCT ) and to provide the basis of deciding the pathogenetic condition and prognosis. METHODS: Eighty - five patients who had been diagnosed with CSCR were grouped by suffering time as below: 32 patients suffered longer than 6mo as the prolonged and 53 patients with CSCR cured within that time. The imaging features of OCT were compared between the above groups.RESULTS:The incidence rate of neuroepithelial serous detachment extent above 500μm associated with pigmentary epithelial detachment in suffering eye and pigmentary epithelial damage in contralateral eye was significantly different between two groups. However, the incidence rate of neuroepithelial serous detachment extent above 4 000μm was not significant difference.CONCLUSlON:OCT could display clearly the change of every layer of retina with simplicity and visibility, which supplies us a new horizon to diagnose and trace CSCR. We could decide the pathogenetic condition and prognosis in accordance with the features of OCT, to provide references for the diagnosis and treatment of CSCR.

Aim To investigate the therapeutic effects of benzoquinone of Averrhoa carambola L. root (BACR) on streptozotocin (STZ)-induced diabetic mice and its mechanism. Methods The diabetic model was induced by intravenous injection of STZ in mice. Drugs were intragastrically administered to mice for 21 days. Fasting blood glucose (FBG) and the change of body weight were measured every 7 days. The levels of the total cholesterol (TC) , triglyceride (TG) and low-density lIPoprotein cholesterol (LDL-C), high-density lIPoprotein cholesterol (HDL-C), monocyte chemoattractant protein-1 (MCP-1) , inter-leukin-IP(IL-lp) in serum and uperoxide dismutase (SOD) , malondialdehyde (MDA), glutathione peroxidase (GSH-Px) in liver tissues were measured after administration. The pathological changes of liver tissues were observed by HE staining. The expression of Tolllike receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) , nuclear factor-kappa B (NF-kB) were observed by immunohistochemistry. Result Compared with model group, the levels of TC, TG, LDL-C, MCP-1, IL-1 p in serum as well as MDA in liver markedly decreased in BACR groups while HDL-C lev-el, the activities of SOD and GSH-Px increased. HE staining showed that BACR improved the pathological condition of liver tissues. The protein expression of TLR4, MyD88, NF-kB were obviously up-regulated. Conclusions BACR could reduce blood glucose, blood lIPid on diabetes mellitus, and its mechanism may be related to inhibiting the release of inflammatory factors and enhancing antioxidant capacity.

In order to explore the effects of Panax notoginoside (PNS) on the expression of transforming growth factor β1 (TGF-β1) and Smad-7 in renal tissues of diabetes, a rat model of diabetic nephropathy was set up by intravenous injection of streptozotocin (STZ). Wistar rats were randomly divided into normal group, diabetic control group, group treated by PNS at low-dosage (PL), group treated by PNS at high-dosage (PH) and group treated by catopril (C), respectively. Fasting blood glucose (FBG), renal index, endogenous creatinine clearance rate (C(Cr)) and urinary albumin (UAlb) in 24 h were examined after 6 weeks. Meanwhile, the expressions of TGF-β1 and Smad7 in renal tissues were immunohistochemically dectected. At the end of the sixth week, FBG, renal index, C(cr), UAlb were all elevated significantly in control group (P<0.01). The expression of TGF-β1 protein was increased while Smad7 protein decreased in renal tissue (P<0.01). However, the treatment with PNS reversed the aforementioned changes in renal tissues of diabetic rats. These results indicate that PNS possess a protective effect on the kidney of diabetic rats and it might protect kidney by inhibiting the expression of TGF-β1 protein and enhancing the expression of Smad7 protein.

Background Glycogen synthase kinase-3β (GSK-3β)plays an important role in glucose metabolism,and it may be affect the occurrence of diabetic retinopathy(DR).ObjectiveThe present study was to investigate the effect of valsartan and fluvastatin on the expression of GSK-3β in retina of diabetes rat model.MethodsDiabetes mellitus models were induced by intrapenetoneal injection of streptozotocin(STZ) in 47 clean Sprague-Dawley(SD) rats and were then randomedly divided into 4 groups.Ten other normal rats were served as normal control group.Sodium carboxy methyl cellulose solution,valsartan,fluvastatin,valsartan+fluvastatin and sodium carboxy methyl cellulose solution was given by oral once per day for 12 weeks respectively in diabetes control group ( n =12),valsartan group ( n =12 ),fluvastatin group ( n =11 ),valsartau + fluvastatin group ( n =12 ) and normal control group.Twelve weeks after administration of drugs,blood glucose was measured and compared among various groups,and the expression of p-GSK-3β ( Ser-9 ) protein in retina was quantified and located by Western blot and immunohistochemistry,respectively.Results Twelve weeks after use of drugs,the level of blood glucose was(5.28±0.30),(26.08±3.33 ),(26.03 ±2.66 ),(25.90± 2.86 ),(25.99 ± 2.14 ) mmol/L in the normal control group,diabetes control group,valsartan,fluvastatin,valsartan + fluvastatin group,respectively,showing a significant difference among the 5 groups ( F =110.74,P＜0.01 ).Western blot showed that the grey value of p-GSK-3β ( Ser-9 ) /β-actin in retina in the diabetic control group was significant higher than the normal group(2.774±0.139 vs 1.927±0.111,q =15.79,P＜0.01 ),and that in valsartan,fluvastatin,valsartan+fluvastatin group was lower than the diabetic control group ( 1.895 ±0.090,2.051 ± 0.113,1.537 ± 0.071 vs 2.774 ± 0.139 ) ( q =1 3.69,13.48,23.06,P ＜ 0.01 ).The grey value of p-GSK-3β (Ser-9)/β-actin in the valsartan+fluvastatin group was declined in comparison with the valsartan group and fluvastatin group ( q =6.67,9.58,P＜0.01 ).Immunohistochemistry showed that the p-GSK-3β(Ser-9) protein was expressed all over the retinal layers and obviously in retinal ganglion cell layer(GCL) in normal control group.But the p-GSK-3β(Ser-9) protein was expressed significantly in diabetic control group.The expression of p-GSK-3β (Ser-9)protein was attenuated both in valsartan and fluvastatin groups and further attenuated in valsartan + fluvastatin group. Conclusions p-GSK-3β (Ser-9) protein is overexpressed in GCL of retina of diabetes rat.Both valsartan and fluvastatin can inhibit the expression of p-GSK-3β (Ser-9) and even getting stronger when they combined.

Tramadol and its metabolites in rat urine were identified by LC-MS(n). Rat urine samples of 0-36 h were collected after ip 9.0 mg x kg(-1) tramadol, then the samples were enriched and purified through solid-phase extraction cartridge. Purified samples were analyzed by LC-MS(n). Possible metabolites were discovered by comparing the full scan and SIM chromatograms of the test samples with the corresponding blanks and analyzing the retention time, quasi-molecular ion and fragment ion of all chromatograms. Nine phase I metabolites and four phase II metabolites were identified in rat urine. One of the metabolites was found first time in living body. The metabolites were formed via the following metabolic pathways: O-demethylation, N-demethylation, hydroxylation, N-oxidation and conjugation. The method can be used to identify tramadol and its metabolites in other animals and human.

In order to explore the effects of Panax notoginoside (PNS) on the expression of transforming growth factor β1 (TGF-β1) and Smad-7 in renal tissues of diabetes,a rat model of diabetic nephropathy was set up by intravenous injection of streptozotocin (STZ).Wistar rats were randomly divided into normal group,diabetic control group,group treated by PNS at low-dosage (PL),group treated by PNS at high-dosage (PH) and group treated by catopril (C),respectively.Fasting blood glucose (FBG),renal index,endogenous creatinine clearance rate (Ccr) and urinary albumin (UAlb) in 24 h were examined after 6 weeks.Meanwhile,the expressions of TGF-β1 and Smad7 in renal tissues were immunohistochemically dectected.At the end of the sixth week,FBG,renal index,Ccr,UAlb were all elevated significantly in control group (P＜0.01).The expression of TGF-β1 protein was increased while Smad7 protein decreased in renal tissue (P＜0.01).However,the treatment with PNS reversed the aforementioned changes in renal tissues of diabetic rats.These results indicate that PNS possess a protective effect on the kidney of diabetic rats and it might protect kidney by inhibiting the expression of TGF-β1 protein and enhancing the expression of Smad7 protein.

Objectives To summarize the characteristics,differential diagnosis and management of incomplete 17 alpha-hydroxylase/17,20-1yase deficiency(17 OHD)of Chinese patients.Methods Six cases of incomplete 17 OHD from Peking Union Medical College Hospital were studied retrospectively through analyzing their clinical data,and the molecular pathogenic mechanism was discussed after literature review.Results Four cases of 46,XX incomplete 17 OHD were reported.The clinical characteristics included female phenotype,various degrees of breast development and absent or sparse axillary/pubic hair, oligomenorrhea or secondary amenorrhea,recurrent luteinized ovarian cysts,hypogonadism with persistent hyperprogesteronemia or high serum 17 alpha-hydroxyprogesterone level,with or without hypokalemic hypertension.There were also 2 cases of 46,XY incomplete 17 OHD,in which ambiguous genitalia were present besides hypokalemic hypertension.Conclusions Incomplete 17 OHD is a very rare form of congenital enzymatic deficiencies of steroid synthesis,which should be included in the differential diagnosis when there are menstrual disorders,sexual infantilism,recurrent ovarian cysts or ambiguous genitalia.Under such circumstances,hyperprogesteronemia offers a valuable clue for further investigation.

Background Though nitric oxide (NO) and NO synthase (NOS) have a critical role in angiogenesis,their effects on corneal neovascularization (CNV) and mechanism need to be further explored.Objective The aim of this study was to explore the effects of NOS and its antagonist,Nw-nitro-L-arginine methyl ester (L-NAME) on experimental CNV in mice,and investigate the influence of NOS and L-NAME on the tube formation of human retinal endothelial cells (RECs) in vitro.Methods The CNV models were established in the left eyes of 36 male BALB/c mice aged 7-8 weeks by application of the filter paper with NaOH in the center of corneas.The mice were randomized into two groups.L-NAME of 10 g/L (0.5 ml) was intraperitoneally injected 1 week before induction of CNV three times a week for three weeks in the mice of the L-NAME injection,and PBS was used in the same way in the control group.CNV was examined under the slit lamp biomicroscope 2,4,7,14 days after NaOH burn.The expression of CD31 in the CNV was assayed to calculate the ratio of CNV area and total corneal area using whole mount technique.The expression of NOS mRNA in the corneal tissue was detected by reverse transcriptase polymerase chain reaction (PCR),and VEGF expression in the human RECs was assayed by Western blot.The vessel formation number of cultured human RECs with or without L-NAME was performed by matrigel in vitro.Grouped t test was used to compare the differences of the parameters between the two groups.Results CNV developed and peaked 2 weeks after the application of NaOH on the mice corneas,and the CNV was obviously less in the L-NAME group compared with the control group.The expression of NOS mRNA in the corneas (NOS mRNA/ GAPDH mRNA)was significantly lower in the L-NAME group than that of the control group 2,4,7 days after CNV induction (t =19.481,t=22.059,t=10.961,all at P＜0.01).The ratio of the CD31 positive area in whole corneal area was 0.59± 0.01 in the L-NAME group,and that of the control group was 0.78±0.10,showing a significant difference between the two groups (t =3.078,P＜0.05).Western blot assay showed that the relative expression of VEGF protein in human RECs was declined in the L-NAME group compared with the control group 0,2,4,7 days,with statistically significant differences in 4 days and 7 days after NaOH burn(t=7.696,t=17.953,both at P＜0.01).The number of vessel network was 46.33±1.86 in the L-NAME group and 64.00±4.51 in the control group,with a significant difference between them (t =3.623,P＜0.05).Conclusions NOS participated in the pathogenesis and aggravation of CNV induced by NaOH.L-NAME arrests CNV formation and human RECs tube formation through down regulating the VEGF expression and NOS activity.

Background Hemorrhagic shock is usually associated with complicated immune and inflammatory responses,which are sometimes crucial for the prognosis.As regulators of the immune and inflammatory system; proliferation,migration,distribution and activation of myeloid-derived suppressor cells (MDSCs) are intimately linked to the inflammation cascade.Methods In a model of severe hemorrhagic shock,thirty-five rats were randomly divided into control,sham,normal saline resuscitation (NS),hypertonic saline resuscitation (HTS),and hydroxyethyl starch resuscitation (HES),with seven in each group.M DSCs were analyzed by flow cytometric staining of CD11b/c+Gra+ in peripheral blood mononuclear cells (PBMC),spleen cell suspensions,and bone marrow nucleated cells (BMNC).Simultaneously,the expressions of arginase-1 (ARG-1) and inducible nitric oxide synthase (iNOS) mRNA in MDSCs were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results In the early stage after hemorrhagic shock,fluid resuscitation and emergency treatment,the MDSCs in the PBMC of NS,HTS and HES groups markedly increased,and MDSCs in BMNC of these groups decreased accordingly,significantly different to the control group.In hemorrhagic shock rats infused with HTS at the early resuscitation stage,MDSCs in PBMC increased about 2 and 4 folds,and MDSCs in BMNC decreased about 1.3 and 1.6 folds,as compared to the sham group respectively,with statistically significant difference.Furthermore,compared to the NS and HES groups,the MDSCs in PBMC of HTS group increased 1.6 and 1.8 folds with statistically significant differences; the MDSCs decrease in BMNC was not significant.However,there was no statistically significant difference in MDSCs of spleen among the five groups.In addition,compared to the control,sham,NS and HES groups,the ARG-1 and iNOS mRNA of MDSCs in PBMC,spleen and BMNC in the HTS group had the highest level of expression,but no statistically significant differences were noted.Conclusions In this model of rat with severe and controlled hemorrhagic shock,small volume resuscitation with HTS contributes to dramatically early migration and redistribution of MDSCs from bone marrow to peripheral circulation,compared to resuscitation with NS or HES.

Objective To analyze the changes of the intima-media thickness(IMT)of carotid and femoral arteries, serum advanced glycosylation end-products(AGEs),and AGEs soluble receptor(sRAGE)after intensively controlling blood glucose, blood pressure, and lipid. Methods One hundred and thirty-two type 2 diabetic patients were divided into 3 groups and followed for 5 years: 20 patients were treated with intensive control of blood glucose and blood pressure, 80 patients with intensive control of blood glucose, blood pressure, and lipid; and 32 patients with conventional therapy. AGEs, sRAGE, and IMT of carotid and femoral arteries were measured and compared among different groups. Results The IMT of carotid and femoral arteries and serum level of AGEs were significantly decreased after intensive treatment. The ratio of sRAGE and HbA1C(sRAGE/HbA1C)were negatively correlated with the mean of HbA1Cin the past five years(r=-0.417, P＜0.001)and the fluctuation of HbA1C(r=-0.309,P＜0.001). Multinomial regression analysis showed that AGEs were the important risk factors of IMT of femoral artery(β=0.152,P=0.068). Conclusion Intensive treatment is significant in controlling the growing IMT of carotid and femoral arteries, while decreasing serum level of AGEs.